2. Academic Validation
  3. Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway

Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway

  • Biochem Biophys Res Commun. 2024 Sep 17:725:150236. doi: 10.1016/j.bbrc.2024.150236.
Chenlei Li 1,  Yan Niu 2,  Jie Chen 3,  Shijia Geng 3,  Peng Wu 3,  Lina Dai 3,  Chongyang Dong 4,  Rujin Liu 1,  Yuanjia Shi 1,  Xiaomeng Wang 1,  Zhanfeng Gao 5,  Xiaoyu Liu 5,  Xi Yang 6,  Shang Gao 7
Affiliations

Affiliations

  • 1 Graduate School of Inner Mongolia Medical University, Inner Mongolia Medical University, Hohhot, 010110, PR China; College of Basic Medicine, Inner Mongolia Medical University, Hohhot, 010110, PR China.
  • 2 Medical Experiments Center, Inner Mongolia Medical University, Hohhot, 010110, PR China.
  • 3 College of Basic Medicine, Inner Mongolia Medical University, Hohhot, 010110, PR China; Medical Experiments Center, Inner Mongolia Medical University, Hohhot, 010110, PR China.
  • 4 Medical Experiments Center, Inner Mongolia Medical University, Hohhot, 010110, PR China; College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, 010110, PR China.
  • 5 The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010110, PR China.
  • 6 College of Basic Medicine, Inner Mongolia Medical University, Hohhot, 010110, PR China; Medical Experiments Center, Inner Mongolia Medical University, Hohhot, 010110, PR China. Electronic address: [email protected].
  • 7 College of Basic Medicine, Inner Mongolia Medical University, Hohhot, 010110, PR China; Medical Experiments Center, Inner Mongolia Medical University, Hohhot, 010110, PR China. Electronic address: [email protected].
PMID: 38897039 DOI: 10.1016/j.bbrc.2024.150236
Abstract

Background: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis.

Methods: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis.

Results: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of apoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK.

Conclusion: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.

Keywords

Atherosclerosis; Focal adhesion kinase; Macrophages; Migration; Paxillin; Plexin D1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12289
    99.74%, FAK Inhibitor
    FAK